Investigation of DNA damage and repair kinetics in normal and tumor tissue may lead to the development of therapy schedules that will take advantage of the differences in these kinetics to improve a tumor patient's response. Because tumors of the central nervous system are essentially dividing cell populations within nondividing normal tissue, differences in their DNA damage and repair kinetics are likely to occur. Therefore, we propose to apply the recently developed technique of viscoelastometry to investigate the DNA damage and repair kinetics of normal rat brain and intracerebral 9L brain tumor after treatment with radiation and chemotherapeutic agents. We will continue our work investigating the DNA damage and repair kinetics of cultured rat 9L brain tumor cells after treatment with radiation and chemotherapeutic agents by analysis of the viscoelastic response of lysates of these cells. We will then evaluate DNA damage and repair kinetics of the normal rat cerebellum and the intracerebral rat 9L brain tumor following in vivo treatment with radiation and drugs. These studies will be extended to include analysis of combination chemotherapy effects and multimodality experiments using both radiation and drugs. These studies should facilitate rational development of brain tumor therapy schedules based on differences of DNA damage and repair kinetics of normal and brain tissue.